Abstract
INTRODUCTION: Sepiapterin reductase deficiency (SRD) is an exceedingly rare neurotransmitter disease caused by an enzyme error involved in the synthesis of tetrahydrobiopterin (BH4). It has been described in nearly 60 cases so far. The clinical manifestations include motor and speech delay, axial hypotonia, dystonia, weakness, oculogyric crises, diurnal fluctuation, and improvement of symptoms during sleep. Molecular genetic analysis can demonstrate pathogenic mutations in the SPR gene, allowing for a definitive diagnosis. Levodopa/carbidopa and 5-hydroxytryptophan are used for treatment. CASE PRESENTATION: We present a 19-year-old male patient who was evaluated for dysarthria, axial hypotonia, limb dystonia, and movement disorder. The parents described the current patient's history with febrile seizures since 9 months of age, as well as speech and neuromotor developmental retardation, which indicated that the disease began in infancy. The basal metabolic work-up was normal except for hyperprolactinemia. The definitive diagnosis of SRD was confirmed by whole exome sequencing (WES) analysis, which revealed a homozygous pathogenic mutation c.655C>T (p.Arg219*) (rs779204655) in the SPR gene. After treatment, we noted significant improvements in dystonia, axial hypotonia, and dysarthria. CONCLUSION: WES analysis offers a more expeditious and dependable method for diagnosing difficult cases exhibiting neurodevelopmental problems and thus renders the possibilities of early management.